The proposed program of research is designed to elucidate the biochemical mechanisms of chemical carcinogenesis in laboratory animals and to develop from these studies certain analytical techniques capable of assessing the exposure of human populations to chemical carcinogens. These investigations will include studies of: the biochemical mechanisms, particularly relative to free radicals, which govern the conversion of carcinogens to their active forms in the target tissues and the relation of these processes to cellular electron transport systems; the roles, in the the process of carcinogenesis, of a specific NO-Fe-protein free-readical induced in rat liver by hepatocarcinogens; the relationship between metabolic conversion of carcinogens and the excretion of carcinogen intermediates in the urine; perfection of techniques based on bacterial mutagenesis and a new electron spin resonance (ESR) technique--hyperfine labelling--to detect, identify and estimate aromatic carcinogen intermediates in urine and tissues; analysis of the free-radicals induced by X-irradiation in normal and neoplastic tissues and in tissues exposed to carcinogens; possible prediction of X-ray sensitivity of tumors from ESR analysis of biopsies; the possible applicability of urine analyses techniques developed in relation to the foregoing studies to studies of the exposure of human populations to chemical carcinogens.